Giuliano Siligardi
Circular Dichroism
Giuliano Siligardi is Principal Beamline Scientist on the Circular Dichroism beamline B23. Prior to joining Diamond, he was a Senior Research Fellow at King’s College London managing the EPSRC and University of London Intercollege Research Centre (ULIRS) Chiroptical Laboratory Centres. His main interest is in Structural Biology, in particular structural relationships in molecular interactions of biologically important molecules such as peptides, proteins, nucleic acids, lipids, carbohydrates and small molecules like therapeutic drugs. Email: Giuliano Siligardi
Tel: +44 (0) 1235 778425
Beamline B23: Circular Dichroism
Key Research Areas
Circular Dichroism, Conformational Analysis, Molecular Recognition, Spectroscopy, Structural Biology
Current Research Interests
Circular Dichroism (CD) is the spectroscopic technique used to study a wide variety of chiral materials such as small molecules (drugs), polymers and biopolymers (nucleic acids, proteins, carbohydrates and lipids). In particular for proteins, knowledge of the structure-function relationship is essential to dissect their mode of action and to identify new targets for novel drug therapeutics.
For rigid and well structured systems, like enzymes and globular proteins, CD is a low-resolution technique compared to NMR and X-ray crystallography. However, a third to half of mammalian proteins have natively disordered structures that are unsuitable for NMR and X-ray crystallography. CD is the technique to study and monitor these systems.
My research has focussed on molecular recognition, the driving force in biological processes such as enzyme catalysis, antigen-antibody recognition, signal transduction, cell signalling and regulation of gene expression. One benefit of understanding molecular recognition is the ability to use structural information to determine affinities of binding interactions. This has clear implications in the design of drug formulation systems to enhance drug stability and delivery.
We have used CD to determine binding affinity because it has the ability to monitor a wide spectral region (140-700nm), enabling us to choose the appropriate wavelength. Other techniques such as IsoThermal Calorimetry (ITC), Surface Plasmon Resonance (SPR), ultra centrifugation, fluorescence, ultrasonic spectroscopy and radio labelling are also used. CD spectroscopy, however, measures the molecular binding affinity directly without labelling or immobilising the sample. The CD beamline will also require a smaller amount of material.
The combination of high photon flux and small beam image size of the Diamond synchrotron CD beamline station will be particularly advantageous in CD time resolved experiments improving the quality of data and reducing substantially the overall time required for measurements. However, the monitoring of these processes in the microsecond time scale is still a formidable challenge. The development of a novel CD time resolved instrument is one of the major projects of our research group.
The extended vacuum-UV region will enable the collection of CD spectra for solutions down to 165nm improving the protein secondary structure content estimation and to 140nm for films and solid phase compounds.
Selected Publications
- "The Role of the phospho CDK2/Cyclin A recruitment site in substrate recognition", K-Y Cheng, M. E. M. Noble, V. Skamnaki, N. R. Brown, E. D. Lowe, L. Kontogiannis, K. Shen, P. A. Cole, G. Siligardi and L. N. Johnson J. Biol. Chem. (2006), 281, 23167 - 23179
- "Fat-free Albumin as a Novel Drug Delivery System", R. Hussain and G. Siligardi Int Jrn of Peptide Research & Therapeutics, (2006) 12, 311-315
- "Identification and characterization of novel lipophilic antimicrobial peptides derived from naturally occurring proteins", R. Hussain, C.L. Joannou and G Siligardi Int Jrn of Peptide Research & Therapeutics, (2006) 12, 269-273
- "Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle", G. Siligardi, B. Hu, B. Panaretou, P.W. Piper, L.H. Pearl and C. Prodromou J. Biol. Chem. (2004), 279, 51989-51998.
- "Structure and Association of Human Lactoferrin Peptides with the Lipopolysaccharide of Escherichia coli", D.S. Chapple, R. Hussain, C.L. Joannou, R.E.W. Hancock, E. Odell, R.W. Evans and G. Siligardi Antimicrobial Agents and Chemotherapy (2004), 48, 2190-2198.